The specific aims of this project are to develop new, efficient, and general syntheses of two classes of known or suspected anticancer plant alkaloids: ellipticine and dimeric indole. It is anticipated that the proposed synthetic methodology will make available gram quantities of these compounds for anticancer screening. Syntheses of the anticancer agent ellipticine and related pyridocarbazoles are proposed which feature highly regioselective reactions between lithioindoles and pyridine dicarboxylic acid anhydrides. The methodology is applied to the synthesis of the highly potent anticancer 9-oxygenated ellipticines and to new ellipticine derivatives for structure-activity screening studies. It is our intent to prepare novel bis-ellipticines as potential nucleic acid polyintercalators. These molecules may represent a new class of highly active anticancer agents. A fundamentally new approach to the construction of complex indole alkaloids in proposed which is applied to the syntheses of dregamine, tabernaemontanine, dihydrocorynantheine, and corynantheidine. The basic synthetic strategy involves sequential Mannich reactions with a preformed piperidylindole ester acetal. The methodology is extended to the conversion of geissoschizine to the 2-acylindole alkaloid vobasine, which comprises half of the anticancer alkaloid tabernamine. It is our long-term objective to make creative contributions to the total synthesis of complex natural products, particularly those possessing medicinal value to mankind. More specifically, it is our research goal to develop new and better chemotherapeutic drugs with which the oncologist can more effectively control human cancer.